In the field of pharmaceutical processing, last generation automatic machines autonomously modify their behavior in order to achieve the best manufacturing quality and productivity despite ever changing process requirements. Mechatronics, as a synergistic integration of electro-mechanical equipment and software control logics, enables such adaptive self-optimizing behaviors. Unfortunately, due to the complex interactions between the different technologies, the final performance of these systems can be effectively validated and optimized only on a physical prototype, with limited possibilities to introduce possible design changes. Therefore, in order to enable validation/optimization of high performance machinery during engineering design stage, a mechatronic Virtual Prototyping (VP) technology is strongly needed. Within this context, the present work discusses a mechatronic VP method based on a Hardware-in-the-Loop, hybrid-process simulation approach, where interactive real-time simulations can effectively assess the real final performance under changing process scenarios. In particular, a case study concerning a high-speed automatic machines for pharmaceutical capsules filling is thoroughly discussed.